Open AccessA multidrug resistance transporter from human MCF-7 breast cancer cells
Author(s) -
Lauren E. Doyle,
Weidong Yang,
Lynne V. Abruzzo,
Tammy Krogmann,
Yan Gao,
Arun K. Rishi,
Douglas D. Ross
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.26.15665
Subject(s) - abcg2 , mcf 7 , daunorubicin , multiple drug resistance , p glycoprotein , atp binding cassette transporter , efflux , cancer cell , biology , mitoxantrone , rhodamine 123 , transporter , abcc1 , cancer research , drug resistance , multidrug resistance associated proteins , cancer , biochemistry , gene , immunology , human breast , leukemia , genetics , chemotherapy
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 663-aa member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.